Epithelial-Mesenchymal Transition Markers in HCVAssociated Hepatocellular Carcinoma: A Multivariate Follow Up Study.

OBJECTIVE: Validated markers to predict recurrence after surgical resection of hepatocellular carcinoma (HCC) are needed. Little data is available regarding epithelial-mesenchymal transition (EMT) markers in HCC. The objective of this study was to investigate the expression of EMT markers and their correlation with clinicopathological variables and survival in hepatitis C virus (HCV)-associated HCC. METHODS: This longitudinal study included 109 cases of HCV-associated HCC treated with surgical resection. Nine different EMT markers (vimentin, E-cadherin, N-cadherin, Stat3, Snail1, Slug, Twist1, Zeb1 and integrin α5) were evaluated on liver tissue from HCC cases. Twenty fresh HCC samples from the studied cases were used for gene expression of EMT markers by quantitative real time polymerase chain reaction (PCR). RESULTS: EMT markers expression was 71%, 25%, 26%, 27%, 9%, 4%, 72%, 47%, 87% for vimentin, E-cadherin, N-cadherin, Stat3 snail1, slug, twist1, Zeb1 and integrin α5 respectively.  EMT mRNA in HCC tissues correlated with protein expression by 50-70%.  Vimentin was independent predictor of large tumor size (P=0.001), high risk of recurrence (HRR) (P=0.006) and shorter disease free survival (P=0.03) in multivariate analysis.  Reduced E-cadherin was a predictor of HRR (P=0.002). CONCLUSION: Vimentin and E-cadherin were the most powerful prognostic EMT markers in HCV-associated HCC in prediction of recurrence.

Human Schistosomiasis mansoni associated with hepatocellular carcinoma in Egypt: current perspective.

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. It was reported to account for about 4.7 % of chronic liver disease in Egyptian patients. The present study aimed at studying the different factors that may be implicated in the relationship of schistosomiasis mansoni with HCC in Egypt. A total of 75 Egyptian patients with primary liver tumours (HCC) were enrolled in this study. They were subjected to full history taking and indirect hemagglutination assay (IHA) for the diagnosis of schistosomiasis. According to the results, the patients were categorized into two groups: Group I: 29 patients with negative IHA for schistosomiasis and hepatitis C virus (HCV) positive with no history or laboratory evidence of previous or current Schistosoma mansoni infection. Group II: 46 patients with positive IHA for schistosomiasis and HCV positive. The significant higher proportion of HCC patients in the present study had concomitant HCV and schistosomiasis (61.3 %) compared to HCC patients with HCV alone (38.7 %) suggesting that the co-infection had increased the incidence of HCC among these patients. Analysis of the age distribution among HCC patients revealed that patients in Group II were younger in age at time of diagnosis of HCC with mean age 57.1 years, as compared to patients in Group I with mean age 64.3 years with a highly significant statistical difference between the 2 groups. HCC in Group II was more common in rural residents while it was more common in urban areas in Group I with a significant statistical difference between the 2 groups. Analysis of the sex distribution among the studied groups showed that HCC was more common in males than females in both groups. As regards the aggression of HCC, it was more commonly multifocal and larger in size in patients with concomitant infection than in patients with HCV alone.

Schistosoma mansoni infection: is it a risk factor for development of hepatocellular carcinoma?

The burden of hepatocellular carcinoma (HCC) in Egypt has been increasing with a doubling in the incidence rate in the past 10 years, which necessitates the investigation of the possible risk factors to its development. The present study aimed at investigating the role of Schistosoma mansoni infection as a risk factor for development of HCC. Five hundred parasite free mice were categorized into four groups: Group I (induction of carcinoma by diethylnitrosamine (DEN)), Group II (DEN+Infection), Group III (Infection) and Group IV (Control). Groups I and II were further subdivided into 4 subgroups according to the dose of DEN given. Serum samples from each group were examined for levels of tumor markers alpha fetoprotein (AFP) and ferritin by ELISA, then mice were sacrificed and subjected to histopathological examination of their livers. These were repeated every week till the end of the experiment. The results of the histopathological examination clarified the role of S. mansoni in enhancing and aggravating the carcinogenic effect of DEN; dysplastic changes appeared earlier, with a higher grade and with a smaller dose of DEN in Group II compared to Group I. Serum levels of tumor markers showed earlier statistically significant differences in Group II than in Group I when compared to Group IV. We conclude that S. mansoni accelerates hepatic dysplastic changes in the presence of other risk factors making cancer appear early and with a more aggressive nature, compared to the same risk in absence of schistosomiasis.